This program project was started in September, 1982. It coordinates biochemical, physiological and pharmacological approaches in order to understand the role of vasoactive hormones and autacoids in circulatory homeostasis. "The Study of the Role of Vasoactive Systems in the Regulation of Blood Pressure and in the Pathogenesis of Hypertension" is the central theme of this program project. Major research emphasis is placed on the joint investigation of vasoactive hormones and autacoids, such as the kallikrein-kinin, renin-angiotensin and tonin-angiotensin II systems, vasopressin, eicosanoids, endothelial-derived factors, adenosine, and atrial natriuretic factor in the regulation of: a) total, cortical and papillary renal blood flow and renal function; b) local systemic vascular resistance and blood pressure; c) renin release; d) neuroendocrine function; and e) vascular reactivity and function. These studies are carried out in both normotensive animals and in different models of hypertension. This program project integrates the research activities and funding of the Hypertension Research Division at Henry Ford Hospital. Four Core Units (Administrative, Radioimmunoassay, Biochemistry, and Biostatistics) will support and facilitate the scientific efforts of the investigators of eight projects. Special expertise is centralized in the core units so that money, space and equipment are used most efficiently. In addition, use of the core facilities removes the burden of day-to-day administrative and methodological concerns from project investigators, so that participants are free to spend their time and energy directly on the experimental parts of their projects. The scientists of the Hypertension Research Division have created an environment of excitement that is conducive to high quality research. In the first three and one-half years of the current program project, significant advances have been made in determining the physiological and physiopathological role of vasoactive hormones and autocoids. The program project provides a better integration of effort in which our continuing collaboration, and sharing of ideas and expertise, accelerates the acquisition of new knowledge on the role of humoral factors in circulatory homeostasis.